This trial is a randomized study of the MitraClip device in heart failure patients with clinically significant functional mitral regurgitation. A hierarchical composite of all-cause mortality and recurrent heart failure hospitalizations is hypothesized to occur at a lower rate with the use of the MitraClip device in addition to optimal standard medical therapy compared to optimal standard of care therapy alone.

Subjects randomized to the Device group will undergo the MitraClip procedure in addition to optimal standard medical therapy

Device: MitraClip

The MitraClip System includes a MitraClip device, a Steerable Guide Catheter, and a MitraClip Delivery System that enables placement of the MitraClip device on the mitral valve leaflets

No Intervention: Control

Subjects randomized to the Control group will receive optimal standard of care therapy alone

Detailed Description:

This study is a clinical evaluation of the safety and effectiveness of the MitraClip System in the treatment of clinically significant functional mitral regurgitation in patients with chronic heart failure. The objective is to further study the safety and effectiveness of the MitraClip System for the treatment of clinically significant functional mitral regurgitation in New York Heart Association Functional Class III or IV chronic heart failure patients.

Eligibility

Ages Eligible for Study:

18 Years to 90 Years

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Age between 18 years and 90 years old

Clinically significant functional mitral regurgitation (moderate-to-severe or severe mitral regurgitation), as defined by European Association of Echocardiography, within 90 days prior to randomization and confirmed by the Echocardiography Core Laboratory

Assessed by the investigator to be on optimal standard of care therapy for heart failure for at least 4 weeks with no dose changes of heart failure drugs (with the exception of diuretics) during the last 2 weeks immediately prior to randomization

Minimum of one documented hospitalization (acute care admission or emergency room visit) for heart failure within 12 months preceding randomization OR values of at least 350 pg/mL for BNP or at least 1400 pg/mL for NT-proBNP after optimal medical and/or device management within 90 days preceding randomization

Left ventricular ejection fraction (LVEF) ≥15% and ≤40% determined by transthoracic echocardiogram within 90 days prior to randomization and confirmed by the Echocardiography Core Laboratory

Left ventricular end diastolic diameter (LVEDD) ≥55 mm determined by transthoracic echocardiogram within 90 days prior to randomization and confirmed by the Echocardiography Core Laboratory

Patient is ambulatory and able to perform a 6MWT with the only limiting factor(s) being due to cardiovascular fitness

Subject agrees to return for all required post-procedure follow-up visits

The subject has been informed of the nature of the study and agrees to the study's provisions, including the possibility of randomization to the Control group, and has provided written informed consent as approved by the respective clinical site's Ethics Committee

Exclusion Criteria:

Mitral regurgitation is primarily due to degenerative disease of the mitral valve apparatus (Degenerative mitral regurgitation), as determined by transesophageal echocardiography

Status 1 heart transplant or prior orthotopic heart transplantation

Introduction of a new heart failure drug class within the last 4 weeks prior to randomization

Cardiovascular hospitalization within the last 2 weeks immediately prior to randomization

Evidence of acute coronary syndrome, transient ischemic attack or stroke within 90 days prior to randomization

Implant of any rhythm management device (i.e., pacemaker, Cardiac Resynchronization Therapy with or without cardioverter-defibrillator (CRT or CRT-D), or Implantable Cardioverter Defibrillator (ICD) within 90 days prior to randomization, or revision of any implanted rhythm management device within 90 days prior to randomization

Need for any cardiovascular surgery

Mitral valve surgery is considered a therapeutic option for the subject

Hypertrophic cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, or any other structural heart disease causing heart failure other than dilated cardiomyopathy of either ischemic or non-ischemic etiology

Hemodynamic instability requiring inotropic support or mechanical heart circulatory support

Active infections requiring current antibiotic therapy

Known hypersensitivity or contraindication to procedural medications which cannot be adequately managed medically

Severe right ventricular failure or severe tricuspid regurgitation

History of bleeding diathesis or coagulopathy or subject who refuses blood transfusions

Pregnant or planning pregnancy within next 12 months. Note: Female patients of childbearing potential need to have a negative pregnancy test performed within 14 days prior to randomization and be adherent to an accepted method of contraception

Concurrent medical condition with a life expectancy of less than 12 months in the judgment of the investigator

Currently participating in another therapeutic or interventional heart failure trial, or in any trial of an unapproved drug or device (Subjects participating in observational studies or registries may be considered as eligible)

Subject belongs to a vulnerable population per investigator's judgment or subject has any kind of disorder that compromises his/her ability to give written informed consent and/or to comply with study procedures

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01772108

Efron B, Tibshirani RJ. An Introduction to the Bootstrap. 1993. Chapman & Hall: New York. EuroQoL Group. The EuroQol - a new facility for the measurement of health-related quality of life. Health Policy 1990;16:199-208.